We seek to develop critical technology to help pre-mature infants and newborns in the first days of life survive and avoid serious airway complications that arise from subglottic stenosis (SGS), the most common acquired anomaly of the larynx in children and the most common abnormality requiring tracheotomy in infants. SGS is preventable and is caused by endotracheal intubation during the critical first days of life. In the premature infant and newborn, this condition may pass undetected or present as a life-threatening event. The ability to better treat and even prevent subglottic stenosis has improved with technical advances in neonatal intensive care, but diagnosis remains a source of continued controversy and debate. The tissues of the subglottis are delicate in nature, easily damaged, and rapidly develop edematous changes, and are predisposed to inflammation, scar formation, and stenosis. Surgical endoscopy has remained the gold standard in the diagnosis of SGS. Unfortunately, surgery requires general anesthesia and is limited to the characterization of the surface anatomy and does not provide detailed analysis of the sub-epithelial tissues. This clinical circumstance is often complicated as the pulmonary, cardiac, and hypoxic thresholds in the newborn population may postpone the evaluation of the airway due to limited tolerances to physiologic stress. In essence, the ultimate challenge in the evaluation of the newborn airway is to minimize diagnostic trauma and physiologic stress while accurately characterizing the laryngeal tissues. Optical Coherence Tomography (OCT) is an imaging modality that utilizes light to produce high-resolution images of living tissues with a resolution in excess of 10 5m. OCT allows for one to distinguish the epithelium from the underlying tissue microstructures based on tissue optical properties with real-time frame rates. Using OCT one can non-invasively characterize living tissues well beyond the current imaging capacities of MRI, CT and ultrasound. We propose to design and construct high speed, high resolution OCT technology combined with 3-D MEMs based probes to image the newborn and infant airways in the neonatal intensive care unit, and define the potential role of OCT in diagnosing the onset and progression of subglottic airway disease in these critically ill patients. First we will optimize the technology in a New Zealand white rabbit model of SGS and compare OCT with conventional microscopy. Then, we will image the subglottic airway in 200 intubated neonates at the UC Irvine-Children's of Hospital of Orange County ICUs and correlate morphologic and structural features obtained with OCT with physiologic and functional variables such as gestational age, weight, and number of failed extubations in order to identify variables that can be used to better predict successful airway extubation, monitor progression of pathophysiologic changes during intubation, and understand the in vivo growth and development of the neonatal airway. We believe we will be able to establish OCT as a viable diagnostic imaging modality that can be used to monitor the neonatal airway and diagnose the early the onset SGS and other ICU acquired laryngeal and upper airway diseases that lead to failed extubation and ultimately tracheostomy.

Public Health Relevance

Subglottic stenosis is the most common indication for tracheostomy in critically ill neonates. Early diagnosis of disease onset may lead to reduction in the incidence of tracheostomy and other airway complications. Development of an office-based treatment technology to diagnosis subglottic stenosis or monitor its development would reduce the need for morbidity and decrease health care costs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL103764-01
Application #
7950291
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Blaisdell, Carol J
Project Start
2010-09-01
Project End
2015-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
1
Fiscal Year
2010
Total Cost
$562,835
Indirect Cost
Name
University of California Irvine
Department
Type
Organized Research Units
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Englhard, Anna S; Wiedmann, Maximilian; Ledderose, Georg J et al. (2018) In vivo imaging of the internal nasal valve during different conditions using optical coherence tomography. Laryngoscope 128:E105-E110
Ajose-Popoola, Olubunmi; Su, Erica; Hamamoto, Ashley et al. (2017) Diagnosis of subglottic stenosis in a rabbit model using long-range optical coherence tomography. Laryngoscope 127:64-69
Sharma, Giriraj K; Chin Loy, Anthony; Su, Erica et al. (2016) Quantitative Evaluation of Adult Subglottic Stenosis Using Intraoperative Long-range Optical Coherence Tomography. Ann Otol Rhinol Laryngol 125:815-22
Coughlan, Carolyn A; Chou, Li-Dek; Jing, Joseph C et al. (2016) In vivo cross-sectional imaging of the phonating larynx using long-range Doppler optical coherence tomography. Sci Rep 6:22792
Manuel, Cyrus T; Tjoa, Tjoson; Nguyen, Tony et al. (2016) Optimal Electromechanical Reshaping of the Auricular Ear and Long-term Outcomes in an In Vivo Rabbit Model. JAMA Facial Plast Surg 18:277-84
Englhard, Anna S; Wiedmann, Maximilian; Ledderose, Georg J et al. (2016) Imaging of the internal nasal valve using long-range Fourier domain optical coherence tomography. Laryngoscope 126:E97-E102
Hussain, Syed; Manuel, Cyrus T; Protsenko, Dmitriy E et al. (2015) Electromechanical reshaping of ex vivo porcine trachea. Laryngoscope 125:1628-32
Lazarow, Frances B; Ahuja, Gurpreet S; Chin Loy, Anthony et al. (2015) Intraoperative long range optical coherence tomography as a novel method of imaging the pediatric upper airway before and after adenotonsillectomy. Int J Pediatr Otorhinolaryngol 79:63-70
Shamouelian, David; Leary, Ryan P; Manuel, Cyrus T et al. (2015) Rethinking nasal tip support: a finite element analysis. Laryngoscope 125:326-30
Volgger, Veronika; Sharma, Giriraj K; Jing, Joseph C et al. (2015) Long-range Fourier domain optical coherence tomography of the pediatric subglottis. Int J Pediatr Otorhinolaryngol 79:119-26

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